Friday, January 25, 2013

Adding To A Feverish Debate

Long time readers may recall that during the summer of 2011 we looked at a study (seeA Feverish Debate) that questioned the conventional wisdom of using antipyretic meds (ibuprofen, acetaminophen or paracetamol, etc) to reduce influenza-related fever.

We conclude that there is an insufficient evidence base to support the use of antipyretics in the treatment of fever from influenza infection.

The limited evidence that does exist suggests that the administration of antipyretics may have the potential to increase the severity of influenza illness and the risk of mortality.

We suggest that randomised controlled trials of the effect of antipyretics in the treatment of influenza are undertaken as an urgent priority.

We are still waiting for results from RCTs to support their concerns, but the idea of letting a fever run its course (at least, up to a point) as part of the body’s natural immune system’s defense isn’t new.

In a another story - also from 2011 - the American Academy of Pediatrics (AAP) released a report on the use of antipyretics in children, suggesting that we ought not over-treat fevers.

Fever in a child is one of the most common clinical symptoms managed by pediatricians and other health care providers and a frequent cause of parental concern. Many parents administer antipyretics even when there is minimal or no fever, because they are concerned that the child must maintain a “normal” temperature.

Fever, however, is not the primary illness but is a physiologic mechanism that has beneficial effects in fighting infection. There is no evidence that fever itself worsens the course of an illness or that it causes long-term neurologic complications.

Today, a study appears in the Journal of Pediatrics on another possible (albeit, rare) adverse effect seen in a small number of young children with fever and dehydration at a hospital in Indiana who received treatment with NSAIDs.

We’ve a press release from Indiana University that warns the administration of NSAIDs to reduce fever may result in AKI - Acute kidney Injury – in young children.

Sick children, especially those with some dehydration from flu or other illnesses, risk significant kidney injury if given drugs such as ibuprofen and naproxen, Indiana University School of Medicine researchers said Friday.

In an article published online Jan. 25 by the Journal of Pediatrics, Jason Misurac, M.D., and colleagues from IU and Butler University reported that nearly 3 percent of cases of pediatric acute kidney injury over a decade could be traced directly to having taken the common nonsteroidal anti-inflammatory drugs, or NSAIDs.

Although relatively few in terms of percentage of total kidney damage cases, the children with problems associated with NSAIDs included four young patients who needed dialysis, and at least seven who may have suffered permanent kidney damage, the researchers said.

"These cases, including some in which patients' kidney function will need to be monitored for years, as well as the cost of treatment, are quite significant, especially when you consider that alternatives are available and acute kidney injury from NSAIDs is avoidable," Dr. Misurac, a fellow in pediatric nephrology, said.

Although such drugs have been linked to kidney damage in small, anecdotal reports, the study reported Thursday is believed to be the first large-scale study of the incidence and impact of acute kidney injury caused by NSAIDs.

The research team evaluated medical records at Riley Hospital for Children at IU Health in Indianapolis from January 1999 through June 2010 and found 1,015 cases in which patients had been treated for acute kidney injury from any cause.

After excluding cases in which the acute kidney injuries could possibly be explained by other factors, such as diseases affecting kidney function, the researchers found 27 cases, or 2.7 percent, in which the only factors were the administration of NSAIDs. In nearly all cases, the NSAIDs were administered before the children were admitted to the hospital. Because many of the 1,015 cases involved multiple potential causes of acute kidney injury, the researchers said the 27 cases are likely an underestimate of the number of cases in which NSAIDs contributed to the kidney damage.

Among the researchers' findings:

Most of the children had been treated with recommended dosages.

All of the children under the age of 5 needed to undergo dialysis temporarily, were more likely than the older children to be placed in an intensive care unit and needed longer hospital stays.

The average cost for hospital and kidney specialist fees in the 27 cases was nearly $13,500, and the costs were much higher for younger children. At least $375,000 was spent on the NSAID-associated kidney injury cases at Riley Hospital over the study period, the researchers said, but billing data for other specialists were not available in the database, suggesting that the actual costs were likely much higher.

NSAIDs affect kidney function by restricting blood flow to the blood-filtering components of the kidneys, which suggests the risks from the drugs are greater among children who are dehydrated due to the effects of their illness, such as vomiting or diarrhea, Dr. Misurac said.

Fever is normal during an infection and not in itself dangerous, he noted, so "one alternative to NSAIDs would be acetaminophen, but another alternative would be no medication at all, at least for a while, to let the body fight the infection."

In a somewhat related story, I’ve written about studies that suggest that the concurrent use of antipyretics may inhibit the immune response when receiving vaccines.

In fact, it has even been theorized that one of the reasons that the elderly often develop less-than-robust immunity from the flu vaccine may be due to their frequent consumption of NSAIDs.

For now the evidence against the use of antipyretics (particularly NSAIDs) for fevers and influenza-like illness is very limited.

But these reports do show that - even after decades of use by hundreds of millions of people – our understanding of the effects of many commonly used over-the-counter medications remains less than complete.